Wednesday, September 5, 2012

More on Nanoparticles causing DNA damage from MOM hips with oxidative stress ( 1 of x in a series)

I was very interested in the recent article which I published on this blog on Monday nite:

Chemical speciation of nanoparticles surrounding metal-on-metal hips

Angela E. Goode , James M. Perkins , Ann Sandison , Chithra Karunakaran , Huikai Cheng , David Wall , John A. Skinner , Alister J. Hart , Alexandra E. Porter , David W. McComb and Mary P. Ryan

Affiliation Information

1. Centre for Clinical Orthopaedics,University College London, London, UK
Chem. Commun., 2012,48, 8335-8337
Abstract can be found in the URL above

I sent that journal article to someone who publishes in this field and he  sent me 3 additional references which are all contained below .  In the past, I have taken time to parse documents which I believe are seminal research in the field.  I believe these three journal articles fall under this seminal research .....I will be doing more detailed writings over the next 5-10 days addressing the key points in these documents.   All of them address nanoparticles (small pieces of metal)  that cross the cell membrane to cause DNA damage causing this  free radical process.

These are really important concepts that may seem confusing at first but I am going to try and make it more intelligible to all of us..... [My normal disclosure: I am neither  a scientist, nor a doctor, nor am I trained in medicine nor any related medical field for that matter.  I hope however, I have enough understanding that we can make some sense out of this.  If I am off a bit in my translation of these ideas into english, apologies in advance.]

Here are the abstracts I will address which were published between 2007-2011:


2011 Nov 6;6(12):824-33. doi: 10.1038/nnano.2011.188.

Signalling of DNA damage and cytokines across cell barriers exposed to nanoparticles depends on barrier thickness.


Bristol Musculoskeletal Research Unit, Clinical Science at North Bristol University of Bristol, Avon Orthopaedic Centre, Southmead Hospital, Bristol.


The use of nanoparticles in medicine is ever increasing, and it is important to understand their targeted and non-targeted effects. We have previously shown that nanoparticles can cause DNA damage to cells cultured below a cellular barrier without crossing this barrier. Here, we show that this indirect DNA damage depends on the thickness of the cellular barrier, and it is mediated by signalling through gap junction proteins following the generation of mitochondrial free radicals. Indirect damage was seen across both trophoblast and corneal barriers. Signalling, including cytokine release, occurred only across bilayer and multilayer barriers, but not across monolayer barriers. Indirect toxicity was also observed in mice and using ex vivo explants of the human placenta. If the importance of barrier thickness in signalling is a general feature for all types of barriers, our results may offer a principle with which to limit the adverse effects of nanoparticle exposure and offer new therapeutic approaches.


2009 Dec;4(12):876-83.

Nanoparticles can cause DNA damage across a cellular barrier.


Bristol Implant Research Centre, Southmead Hospital, Bristol, UK.


The increasing use of nanoparticles in medicine has raised concerns over their ability to gain access to privileged sites in the body. Here, we show that cobalt-chromium nanoparticles (29.5 +/- 6.3 nm in diameter) can damage human fibroblast cells across an intact cellular barrier without having to cross the barrier. The damage is mediated by a novel mechanism involving transmission of purine nucleotides (such as ATP) and intercellular signalling within the barrier through connexin gap junctions or hemichannels and pannexin channels. The outcome, which includes DNA damage without significant cell death, is different from that observed in cells subjected to direct exposure to nanoparticles. Our results suggest the importance of indirect effects when evaluating the safety of nanoparticles. The potential damage to tissues located behind cellular barriers needs to be considered when using nanoparticles for targeting diseased states.


2007 Jul;28(19):2946-58. Epub 2007 Mar 1.

The effect of nano- and micron-sized particles of cobalt-chromium alloy on human fibroblasts in vitro.


Bristol Implant Research Centre, Avon Orthopaedic Centre, Southmead Hospital, Bristol BS10 5NB, UK.


Wear debris from metal on polyethylene joint replacements causes asceptic loosening as a result of an inflammatory reaction of macrophages to micron-sized particles. Metal on metal implants, which generate nanoparticles, have been reintroduced into surgical practise in order to avoid this problem. There is a current concern about possible long-term effects of exposure to metal particles. In this study, the cytotoxic and genotoxic effects of nanoparticles and micron-sized particles of cobalt chrome alloy have been compared using human fibroblasts in tissue culture. Nanoparticles, which caused more free radicals in an acellular environment, induced more DNA damage than micron-sized particles using the alkaline comet assay. They induced more aneuploidy and more cytotoxicity at equivalent volumetric dose. Nanoparticles appeared to disintegrate within the cells faster than microparticles with the creation of electron dense deposits in the cell, which were enriched in cobalt. The mechanism of cell damage appears to be different after exposure to nanoparticles and microparticles. The concept of nanotoxicology is, therefore, an important consideration in the design of future surgical devices.


I will start with the 2007 journal article  first and will post other items as they come up.  the sequence will be numbered so you can follow along if you choose.

1 comment:

  1. You are doing a fab job.Its not always easy to present a thing when you are not from a similar field.I will be waiting for you articles on nanotubes.